Age associated losses of strength occur slowly over the adult lifespan. Most research has focused on what occurs in the elderly. However, the primary processes start at a much earlier age. Changes in strength are associated with functional disability and frailty in the elderly. In young and middle-aged workers, it is a contributing factor to work related injuries and for some occupations, job performance. The causes of age related strength losses are now being studied and are multifactoral. Much of current scientific interest is on age changes in muscle and the loss of muscle with age that has been referred to as sarcopenia, The focus of work on sarcopenia has been on the elderly where the greatest changes in muscle mass and strength manifest. However, by age 50 the average individual has lost 10% of their maximal strength. While sarcopenia is clearly a major factor in strength loss, there are other contributors to the changes in maximal function. To understand sarcopenia these other factors need to be studied. Furthermore, less is known about the causes in young and middle aged adults where other factors may be more important than sarcopenia. A better understanding of these causes can lead to more directed methods of prevention. Our goal is to understand the time course of strength loss, factors that contribute to the loss, what degree the exercise response differs between old and young individuals, and what forms of motivators and alternative exercise programs might impact on the losses. First are descriptive studies using the Baltimore Longitudinal Study of Aging (BLSA). These studies focus on describing the characteristic losses that occur in muscle strength mass, and physical functioning that occur with aging by examining the entire adult lifespan. Over the past year, have shown that declining muscle strength and rate of change of muscle strength are independent contributors to mortality in men when considering age, physical activity and muscle mass. In addition, muscle power is a stronger independent contributor to mortality in men than is muscle strength though both have independent contributions to mortality. In addition, we reported genetic studies showing that IGF-II genotype was found to be related to muscle strength but not muscle mass. This is consistent with the mortality data, where muscle mass and muscle strength have common and different effects on outcome. We also found that testosterone and free testosterone index had modest contributions toward muscle strength independent of muscle mass. Their action through body composition appeared to be more related to fatness than directly to muscle mass. In addition, socioeconomic status may be an important influence on the age-associated relationship with muscle strength in African Americans with younger, lower socioeconomic subjects being markedly weaker than higher socioeconomic subjects of the same age. Second are reports from an intervention comparing the response to resistive strength training between young and old subjects. The main finding of the study was that exercise response to resistive training is very similar in young and old subjects. In this reporting period, we found that myostatin mRNA decreases in response to heavy resistance strength training. Myostatin is of interest because high levels are associated with prominent muscle atrophy and in the elderly with the development of frailty. Our observation demonstrates that resistive training can lower the level of myostatin within muscle and thus alter one factor that is involved with the loss of muscle mass. In addition,we observed differences in skeletal muscle gene expression when looking at approximately 4000 genes known to be involved with muscle. Sex had the strongest influence on muscle gene expression, with differential expression (>1.7-fold) observed for ~200 genes between men and women (~75% with higher expression in men). Age contributed to differential expression as well, as approximately 50 genes were identified as differentially expressed (>1.7-fold) in relation to age, representing structural, metabolic, and regulatory gene classes. Sixty-nine genes were identified as being differentially expressed (>1.7-fold) in all groups in response to strength training, and the majority of these were down regulated. These results provide evidence for significant differences in skeletal muscle gene expression between men and women, between young and older individuals, and as a result of strength training. Thus, while the response to strength training may be similar by age, there are clear differences in muscle responsiveness as represented by gene expression. Two interventions were reported that examined alternative strategies for exercise intervention in subject with osteoarthritis of the knee. First was electromyostimulation, a passive activation of the knee extensor muscles using an electric stimulator. Typically, it is used to generate near maximal forces or added to active contractions to increase the force generated. This form of treatment has been successfully used in treating patients following knee surgery. Our goal was to test a protocol that used NMES at much lower force levels, to make the stimulation more acceptable (i.e. with less or no pain), and to minimize the likelihood of injury in individuals with osteoarthritis of the knee. We hypothesized that weak elderly subjects do not require maximal force generation to improve strength. The NMES group used a portable electrical muscle stimulator to incrementally increase the intensity of isometric contraction over 12 weeks up to 20-40% of their maximal voluntary strength. We found an increase in muscle strength in response to this passive activity, and a decline in knee pain immediately following the treatment (though not a sustained effect). The second approach was to use homebased pedometer driven motivational program resulted in improved walking, increased knee extensor strength, and modest functional improvements. Both alternative approaches to exercise gave indication that they may be a useful alternative to more traditional exercise programs. What we have demonstrated is the feasibility for using these (and similar) approaches in patients with osteoarthritis, and potentially in others with some levels of disability. The work in the National Guard will determine whether a simple motivational tool when properly implemented might increase participation in healthy subjects.